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1.2.1 Gastro-oesophageal reflux disease is common in children

with ND

Gastro-oesophageal reflux refers to the retrograde passage of stomach contents into the oesophagus. This physiological phenomenon can occur normally in healthy children and adults at any time, particularly after eating. In health, it lasts for short periods of time only and is asymptomatic (Vandenplas et al., 2009). This becomes a disease process when it causes recurrent symptoms or complications (Vandenplas et al., 2009).

The high incidence of GORD in children with ND is well recognised. Up to 75% of those with severe CP have GORD, with contributory factors including decreased lower oesophageal sphincter tone, delayed gastric emptying, impaired oesophageal motility, scoliosis, seizures, medications, and poor positioning (Gustafsson & Tibbling, 1994; Mazzoleni et al., 1991; Peter B. Sullivan, 2008). Somerville and colleagues found evidence of chronic oesophagitis on upper airway endoscopy in 57% of 182 children with severe developmental disability (Somerville et al., 2008). Respiratory symptoms and complications of GORD may include cough, wheeze, shortness of breath and recurrent pneumonia (Boesch et al., 2006). However, it is important to consider that although these sequelae may be a direct result of GORD through recurrent micro-aspiration or direct stimulation of the distal oesophagus, they may also be unrelated. It can be difficult to establish a causal relationship (Mansfield & Stein, 1978). The risk of micro-aspiration with GORD is potentially increased due to impaired laryngeal sensation, known to be associated with recurrent gastro-oesophageal reflux (Aviv et al., 2000). Equally, respiratory symptoms themselves can cause/increase GORD. This ‘chicken and egg’ scenario results in limitation of our understanding of the effects of GORD on the airway and has been discussed at length in the literature (Shields, Bateman, McCallion, van Wijk, & Wenzl, 2011).

GORD can be particularly difficult to diagnose in children with ND, due to difficulties in communication and interpretation of behaviour. Clinical investigations including upper gastro-intestinal contrast studies, upper gastrointestinal endoscopy, pH studies and newer modalities such as impedance

monitoring are all used by gastroenterologists to aid diagnosis (Vandenplas et al., 2009) (Peter B. Sullivan, 2008).

1.2.2 Swallowing dysfunction is common in children with

neurodisability

Dysfunctional swallowing (from oral and pharyngeal motor impairment) is also common in children with ND (Andrew et al., 2012). This can present with a wide range of symptoms, from subtle feeding difficulties and nutritional deficiencies to overt symptoms of aspiration and recurrent lower respiratory tract infection. A ‘safe swallow’ requires a level of oral motor skill to ensure adequate oral food preparation, formation of a bolus and a co-ordination of oral, pharyngeal and oesophageal muscles, enabling safe passage of the bolus into the stomach with accompanying airway protection from aspiration. Estimations of swallowing dysfunction frequency (as assessed by videofluoroscopy) in children with severe ND can be up to 70%, depending on the population studied (Andrew et al., 2012; Arvedson, Rogers, Buck, Smart, & Msall, 1994; Mirrett, Riski, Glascott, & Johnson, 1994; Somerville et al., 2008; K. Weir, McMahon, Barry, Masters, & Chang, 2009; K. A. Weir et al., 2011). An important observation from videofluoroscopy studies is the high frequency of silent, symptomless aspiration in this group, leading many authors to conclude that any child with neurological dysfunction who presents with feeding difficulties should undergo a videofluoroscopic assessment (Andrew et al., 2012; K. A. Weir et al., 2011).

1.2.3 Differentiation of direct and reflux aspiration

Pulmonary aspiration is the abnormal passage of the contents of the upper airway into the lower airway. The clinical consequences of recurrent aspiration can range from recurrent cough and wheeze and recurrent lower respiratory tract infection to acute life threatening events and catastrophic pulmonary injury and death in cases of large volume aspiration (Boesch et al., 2006). The commoner clinical scenario of repeated small-volume aspiration can potentially lead to chronic pulmonary disease, as discussed in Section 1.5.

saliva into the lungs), reflux-aspiration (aspiration of refluxed stomach contents into the lungs) or a combination of both. It is important to be able to differentiate direct and indirect aspiration as the clinical management is distinct, as detailed in Sections 1.2.4 and 1.2.5. In a research setting, we are unable to fully assess the outcomes of intervention without being able to assess the relative contributions of the different types of aspiration to clinical symptoms.

1.2.4 Clinical management of direct aspiration

Direct aspiration can include aspiration of solid food, liquid or saliva. Diagnosis of direct aspiration is discussed in Section 1.3. Following diagnosis, interventions such as alteration of food consistency and optimal positioning of the child for feeding can be useful. Ideally, feeding interventions should be undertaken following multi-disciplinary assessment, as discussed in Section 1.1.6.3.

In patients where oral feeding cannot be maintained (due to risk of direct aspiration or inadequate nutritional intake) percutaneous gastrostomy feeding may be considered. This intervention potentially eliminates the risk of direct aspiration of food. However, it does not alter the frequency of salivary aspiration. There is little documented about the frequency of salivary aspiration and its direct clinical consequences in the literature, due to limitations in diagnostic abilities, as discussed in Section 1.3. However, salivary aspiration is potentially an important contributory factor in aspiration lung disease in children with ND, particularly due to the potential for instillation of pathogenic bacteria from the oral cavity into the lungs in a group who may have poor oral and dental hygiene, increasing the incidence of anaerobic pneumonia (Wallis & Ryan, 2012).

There are various medical and surgical options for management of salivary aspiration. Anti-cholinergic medications (such as glycopyrrolate), which interact with peripheral muscarinic receptors, are commonly used in the management of sialorrhoea (Eiland, 2012). The side effect profile of these medications, which includes anti-cholinergic symptoms and mucous plugging, and the limited evidence base for their use are discussed in Chapter 3. Most of the literature concerning their use has focussed on control of sialorrhoea rather than improving

respiratory outcomes, perhaps again because of the difficulties in diagnosing salivary aspiration and limited data regarding the role of salivary aspiration in causality of respiratory symptoms (Eiland, 2012; Zeller, Davidson, Lee, & Cavanaugh, 2012; Zeller, Lee, Cavanaugh, & Davidson, 2012).

Surgical management options include sub-mandibular and parotid gland botulinum toxin or removal of sub-mandibular glands and ligation of parotid glands (Ellies et al., 2002; Walshe, Smith, & Pennington, 2012; Wilken, Aslami, & Backes, 2008). The evidence base for these interventions is similarly limited and they are used with variable success, particularly from a respiratory symptom perspective (as discussed in Section 3.5 of this thesis).

1.2.5 Clinical management of reflux aspiration

The aim of reflux aspiration management is ideally to stop the reflux of gastric contents into the oesophagus. However, a secondary aim may be to minimise symptoms caused by the refluxate by neutralising the acidity of the stomach contents. Management options include lifestyle, pharmacological and surgical approaches. Simple measures aimed at reducing the frequency of reflux events include changing the feed volume and frequency, altering the child’s position for feeding, and thickening feeds (Vandenplas et al., 2009).

Where these simple measures fail, there are various pharmacological options. Pro-kinetic agents, such as domperidone and erythromycin, are commonly used with the aim of encouraging prompt gastric emptying. However, the evidence for their efficacy in children is limited (as discussed in Section 3.5) (Pritchard, Baber, & Stephenson, 2005; Vandenplas et al., 2009). Proton pump inhibitors are often used for reflux symptom control and treatment of oesophagitis, limiting the acidity of the refluxate by blocking the proton pump (H+/K+ ATPase) of the gastric parietal cells. There is some evidence that these are effective when used for the purposes of gastroenterological reflux symptom control (Hassall, 2005). However, their role in the management of reflux aspiration is questionable because in the context of chronic, small-volume reflux-aspiration the refluxate is likely to be mildly acidic or neutral pH on reaching the lower airway (as

inhibitors, possibly due to gastric bacterial overgrowth (Fohl & Regal, 2011; Theisen et al., 2000).

Where medical management fails, patients are referred for surgical assessment for anti-reflux procedures. Fundoplication is the commonest anti-reflux procedure. In the United States, children with ND represent approximately 40% of the paediatric population undergoing fundoplication (Lasser, Liao, & Burd, 2006). This technique involves wrapping the upper part of the stomach (the fundus) around the lower end of the oesophagus, creating a muscular tunnel, aiding the lower oesophageal sphincter in preventing reflux of stomach contents into the oesophagus (Shields et al., 2011). However, surgery associated morbidity and mortality rates are higher in children with ND and primary failure and ‘re-do’ fundoplication rates are increased (Hassall, 2005; Lasser et al., 2006; Pearl et al., 1990; C. D. Smith et al., 1992; Subramaniam & Dickson, 2000; Wockenforth, Gillespie, & Jaffray, 2011). Results from studies on respiratory outcomes, gastrointestinal outcomes, and quality of life after fundoplication have been contradictory and some surgical centres are now advocating increased scrutiny in selecting children who may benefit from fundoplication (Fonkalsrud et al., 1998; Goldin, Sawin, Seidel, & Flum, 2006; Martinez, Ginnpease, Caniano, Vinocur, & Golladay, 1992; Shields et al., 2011; C. D. Smith et al., 1992; Rajendu Srivastava et al., 2009). Other options used in the surgical management of GORD include jejunal feeding and gastro-oesophageal dissociation (Verey & Cusick, 2008; Wales et al., 2002; Wockenforth et al., 2011). High quality prospective trials are needed to assess the outcomes of these interventions in children with ND, with careful attention being paid to patient group specific outcome measures (Vernon-Roberts & Sullivan, 2007).